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J Cancer 2023; 14(9):1499-1514. doi:10.7150/jca.82370 This issue Cite

Research Paper

A five-cuproptosis-related LncRNA Signature: predicting prognosis, assessing immune function & drug sensitivity in lung squamous cell carcinoma

Hongtao Zhao¹, Lei Wu², Qinyuan Liao¹, Peiluo Huang^1,3, Ruonan Sun¹, Xiuzhen Yang^4✉, Juan Du^1✉

1. Department of Immunology, College of Basic Medicine, Guilin Medical University, Guilin 541199, Guangxi, China.
2. College of continuing education, Guilin Medical University, Guilin 541004, China.
3. College of pharmacy, Guilin Medical University, Guilin 541199, China.
4. Department of clinical laboratory, Zibo Central Hospital, Zibo 255036, China.

✉ Corresponding authors: yangxz770com; sunnydujuanedu.cn.

Abstract

Lung squamous cell carcinoma has so far lacked effective targets for diagnosis and treatment. In cancer research, long noncoding RNAs (LncRNAs) emerge as novel therapeutic targets and biomarkers. Cuprophosis is a new death type involving multiple biological processes in tumor cells. Here, we aimed to explore whether Cuprophosis-related lncRNAs could be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients. The Cancer Genome Map (TCGA) was used to obtain genome and clinical data, and Cuprophosis-relevant genes were found in the literature. A cuproptosis-related lncRNA risk model was built using co-expression analysis, univariate/multivariate Cox regression, and LASSO analysis. The survival analysis was used to assess the model's prognostic value. The univariate and multivariate Cox regression analyses were performed to determine whether risk score, age, gender, or clinical stages could be used as independent prognostic factors. Gene Set Enrichment Analysis and mutation analysis were performed on differentially expressed mRNA between high-risk and low-risk groups. The (TIDE) algorithm was used to conduct immunological functional analysis and drug sensitivity testing. Five cuproptosis-related LncRNAs were identified, and the selected LncRNAs constructed a prognosis model. According to the Kaplan-Meier survival analysis, the overall survival time for patients in the high-risk group was shorter than for those in the low-risk group. For LUSC patients, the risk score serves as an independent prognostic indicator. The GO and KEGG enrichment analysis revealed that the differentially expressed mRNAs between the high- and low-risk groups were enriched in several immune-related processes. The enrichment score of differentially expressed mRNAs in the high-risk group is higher than that of the low-risk group in multiple immune function pathways, including the IFN-γ and MHC I pathways. The Tumor Immune Dysfunction and Exclusion (TIDE) test revealed that the high-risk group was more likely to experience immune escape. The drug sensitivity analysis showed that patients with low-risk ratings were likely to respond to GW441756 and Salubrinal. In contrast, patients with higher risk scores were more responsive to dasatinib and Z-LLNIe CHO. The 5-Cuprophosis-related lncRNA signature can be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients.

Keywords: Cuproptosis, LncRNA, LUSC, Prognostic model, Drug sensitivity

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